Personalized medicine is currently hampered by the lack of flexible drug formulations. Especially for pediatric patients, manual compounding of personalized drug formulations by pharmacists is required. Three-Dimensional (3D) printing of medicines, which enables small-scale manufacturing at the point-of-care, can fulfill this unmet clinical need. This study investigates the feasibility of developing a 3D-printed tablet formulation at the point-of-care which complies to quality requirements for clinical practice, including bioequivalence. Development, manufacturing, and quality control of the 3D-printed tablets was performed at the manufacturing facility and laboratory of the department of Clinical Pharmacy and Toxicology at Leiden University Medical Center. Sildenafil was used as a model drug for the tablet formulation. Along with the 3D-printed tablets a randomized, an open-label, 2-period, crossover, single-dose clinical trial to assess bioequivalence was performed in healthy adults. Bioequivalence was established if areas under the plasma concentration curve from administration to the time of the last quantifiable concentration (AUC0-t) and maximum plasma concentration (Cmax) ratios were within the limits of 80.00–125.00%. The manufacturing process provided reproducible 3D-printed tablets that adhered to quality control requirements and were consequently used in the clinical trial. The clinical trial was conducted in 12 healthy volunteers. The 90% confidence intervals (CIs) of both AUC0-t and Cmax ratios were within bioequivalence limits (AUC0-t 90% CI: 87.28–104.14; Cmax 90% CI: 80.23–109.58). For the first time, we demonstrate the development of a 3D-printed tablet formulation at the point-of-care that is bioequivalent to its marketed originator. The 3D printing of personalized formulations is a disruptive technology for compounding, bridging the gap toward personalized medicine.
|Number of pages||7|
|Journal||Clinical Pharmacology and Therapeutics|
|Early online date||10 Feb 2023|
|Publication status||Published - May 2023|
Bibliographical noteFunding Information:
This study was funded by a research grant of the Dutch Ministry of Health, Welfare, and Sport (Foundation NFKC).
© 2023 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.